Background: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent
periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely
understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent
mechanism.
Methods: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable
coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled,
and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function
was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses
(10−6
, 10−5
, 10−4 mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating
markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography.
The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter
following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235).
Results: 75 patients were enrolled. Following angiography, 60 patients (mean ± SD age 57.5 ± 8.5 years; 80%
male) were eligible and completed the protocol (n = 30 RIPC, n = 30 sham). The mean percentage change in
coronary luminal diameter was −13.3 ± 22.3% and −2.0 ± 17.2% in the sham and RIPC groups respectively
(difference 11.32%, 95%CI: 1.2– 21.4, p = 0.032). This remained significant when age and sex were included as
covariates (difference 11.01%, 95%CI: 1.01– 21.0, p = 0.035). There were no between-group differences in
endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function.
Conclusions: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This
endothelium-dependent mechanism may contribute to the cardioprotective effects of RIP
